Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BET inhibitor Pelabresib and AR inhibitor enzalutamide perturbed pathways in prostate cancer CRPC PDX LuCaP 77CR

ABSTRACT: To study the effect of inhibiting AR and HNF1A/HNF4G activity either alone or in combination on the growth of CRPC PDX LuCaP 77CR.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253805 | GEO | 2025/01/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

BET inhibitor Pelabresib and AR inhibitor enzalutamide perturbed pathways in prostate cancer CRPC PDX LuCaP 35CR

Project description:To study the effect of inhibiting AR and HNF1A/HNF4G activity either alone or in combination on the growth of CRPC PDX LuCaP 35CR

2025-01-18 | GSE254665 | GEO

BET inhibitor Pelabresib and AR inhibitor enzalutamide perturbed pathways in prostate cancer CRPC PDX LuCaP 35CR

Project description:BET inhibitor Pelabresib and AR inhibitor enzalutamide perturbed pathways in prostate cancer CRPC PDX LuCaP 35CR

| PRJNA1071482 | ENA

BET inhibitor Pelabresib and AR inhibitor enzalutamide perturbed pathways in prostate cancer CRPC PDX LuCaP 77CR

Project description:BET inhibitor Pelabresib and AR inhibitor enzalutamide perturbed pathways in prostate cancer CRPC PDX LuCaP 77CR

| PRJNA1067152 | ENA

Gene expression profile at single cell level in prostate cancer PDX, LucaP 70CR treated with Bromo- and -extraterminal domain (BET) inhibitor Pelabresib and vehicle control

Project description:We used single-cell RNA-sequencing to evaluate the effect of BET inhibitor, pelabresib on AR and HNF1A/HNF4G regulated transcriptome in prostate cancer PDX

2025-01-18 | GSE253806 | GEO

Saracatinib synergizes with enzalutamide to downregulate AR activity in CRPC.

Project description:Prostate cancer (PCa) remains the most diagnosed non-skin cancer amongst the American male population. Treatment for localized prostate cancer consists of androgen deprivation therapies (ADTs), which typically inhibit androgen production and the androgen receptor (AR). Though initially effective, a subset of patients will develop resistance to ADTs and the tumors will transition to castration-resistant prostate cancer (CRPC). Second generation hormonal therapies such as abiraterone acetate and enzalutamide are typically given to men with CRPC. However, these treatments are not curative and typically prolong survival only by a few months. Several resistance mechanisms contribute to this lack of efficacy such as the emergence of AR mutations, AR amplification, lineage plasticity, AR splice variants (AR-Vs) and increased kinase signaling. Having identified SRC kinase as a key tyrosine kinase enriched in CRPC patient tumors from our previous work, we evaluated whether inhibition of SRC kinase synergizes with enzalutamide or chemotherapy in several prostate cancer cell lines expressing variable AR isoforms. We observed robust synergy between the SRC kinase inhibitor, saracatinib, and enzalutamide, in the AR-FL+/AR-V+ CRPC cell lines, LNCaP95 and 22Rv1. We also observed that saracatinib significantly decreases AR Y534 phosphorylation, a key SRC kinase substrate residue, on AR-FL and AR-Vs, along with the AR regulome, supporting key mechanisms of synergy with enzalutamide. Lastly, we also found that the saracatinib-enzalutamide combination reduced DNA replication compared to the saracatinib-docetaxel combination, resulting in marked increased apoptosis. By elucidating this combination strategy, we provide pre-clinical data that suggests combining SRC kinase inhibitors with enzalutamide in select patients that express both AR-FL and AR-Vs.

| S-EPMC10348659 | biostudies-literature

Targeting KDM4A-AS1 represses AR/AR-Vs deubiquitination and enhances enzalutamide response in CRPC.

Project description:Castration-resistant prostate cancer (CRPC) is a highly malignant type of advanced cancer resistant to androgen deprivation therapy. One of the important mechanisms for the development of CRPC is the persistent imbalanced regulation of AR and AR splice variants (AR/AR-Vs). In this study, we reported KDM4A-AS1, a recently discovered lncRNA, as a tumor promoter that was significantly increased in CRPC cell lines and cancer tissues. Depletion of KDM4A-AS1 significantly reduced cell viability, proliferation, migration in vitro, and tumor growth in vivo. We found that by binding to the NTD domain, KDM4A-AS1 enhances the stability of USP14-AR/AR-Vs complex, and promoted AR/AR-Vs deubiquitination to protect it from MDM2-mediated ubiquitin-proteasome degradation. Moreover, KDM4A-AS1 was found to enhance CRPC drug resistance to enzalutamide by repressing AR/AR-Vs degradation; antisense oligonucleotide drugs targeting KDM4A-AS1 significantly reduced the growth of tumors with enzalutamide resistance. Taken together, our results indicated that KDM4A-AS1 played an important role in the progression of CRPC and enzalutamide resistance by regulating AR/AR-Vs deubiquitination; targeting KDM4A-AS1 has broad clinical application potential.

| S-EPMC8755543 | biostudies-literature

RNA seq analysis of LuCaP Prostate Cancer Patient-Derived Xenografts

Project description:We assembled a prostate xenograft interactome from a large data set with 128 RNA sequencing expression profiles generated through administration of 13 small molecule perturbagens in vivo to 5 distinct and genetically diverse LuCaP xenograft lines (LuCaP 73, LuCaP77, LuCaP 78, LuCaP 81, LuCaP 147), with half of the xenograft samples collected from hosts castrated for 1 week.

2023-01-23 | GSE184427 | GEO

mCRPC LuCaP PDXs ChIP-seq

Project description:Informed consent was obtained to collect human mCRPC tissues and generate the patient-derived xenograft tumors as described previously (Labrecque et al., 2019; Nguyen et al., 2017). The study was approved by the University of Washington Human Subjects Division institutional review board (no. 39053). All animal studies were approved by University of Washington IACUC and performed according to NIH guidelines. Molecular characterization of AR+ mCRPC LuCaP PDXs 70CR, 78CR, 81CR, 96CR, 105CR, 136CR and 147CR was previously described (Labrecque et al., 2019; Nguyen et al., 2017). LuCaP PDX 167CR was established from a liver metastasis of 77-year-old Caucasian male who died of abiraterone-, carboplatin- and docetaxel-resistant CRPC. LuCaP 167CR expresses AR, responds to castration and is negative for synaptophysin. PDX cellular morphology recapitulates the original liver metastasis (Supplementary Figure S8A).

2022-04-06 | GSE163220 | GEO

mCRPC LuCaP PDXs ChIP-seq

Project description:mCRPC LuCaP PDXs ChIP-seq

| PRJNA685358 | ENA

HNF4G, AR, FOXA1, H3K4me1, H3K27acetyl binding sites upon knockdown and overexpression of HNF4G in 22Rv1 and LNCaP prostate cancer cells respectively

Project description:HNF4G is a gastrointestinal tissue enriched master transcriptional regulator seen overexpressed in a subset of prostate cancer. Here we have mapped binding sites of HNF4G, AR, Foxa1, H3K4me1, H3K27acetyl upon knockdown and overexpression of HNF4G in in 22Rv1 and LNCaP cells respectively

2017-11-01 | GSE85558 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data